CN110882228A

CN110882228A - Epiputidine enteric-coated preparation

Info

Publication number: CN110882228A
Application number: CN201911207452.6A
Authority: CN
Inventors: 夏献民; 潘颂华; 周伟
Original assignee: Nanjing Ho Han Pharmaceutical Technology Co Ltd
Current assignee: Wuhan Yi Bio Technology Co.,Ltd.
Priority date: 2019-11-29
Filing date: 2019-11-29
Publication date: 2020-03-17

Abstract

The invention discloses an ipipimaric peptide enteric-coated preparation which is prepared from the following raw materials in parts by weight: the Yipiwu peptide enteric-coated preparation is characterized by comprising 15-20 parts of Yipiwu peptide bulk drug, 1.5-2 parts of dextrin, 1-1.5 parts of calcium sulfate, 1.8-2 parts of starch, 0.1-0.5 part of talcum powder, 2-2.5 parts of starch slurry, 4-5.3 parts of croscarmellose sodium, 0.5-1 part of acrylic resin I, 0.5-1 part of acrylic resin II, 12-15 parts of ethanol solution, 0.2-0.4 part of propylene glycol, 0.3-0.5 part of castor oil, 0.1-0.5 part of magnesium stearate and 0.03-0.05 part of Chinese wax, wherein the Yipiwu peptide bulk drug is produced by a chemical synthesis and high performance liquid chromatography separation refining process, has stable biological activity, simple pilot test process and low cost, does not disintegrate when being eroded by gastric juice, can disintegrate quickly when being eroded by intestinal juice, and is convenient for absorption of effective substances, meanwhile, the preparation has high stability, can be stored for a long time, has common raw materials, and is suitable for large-scale production.

Description

Epiputidine enteric-coated preparation

Technical Field

The invention belongs to the field of enteric-coated preparations, and particularly relates to an ipipimu peptide enteric-coated preparation.

Background

The inflammation is infectious inflammation caused by infection or non-infectious inflammation caused by infection, generally, the inflammation is beneficial and is automatic defense reaction of a human body, but sometimes, the inflammation is harmful, such as attack to the tissues of the human body, inflammation occurring in transparent tissues and the like, so that the phenomenon is inhibited by the appearance of anti-inflammatory drugs, most of the common anti-inflammatory drugs are oral drugs, but effective substances in part of the oral drugs can damage gastric mucosa, the enteric-coated preparation is a preparation which is not disintegrated in gastric juice and can be disintegrated and absorbed in intestinal juice, and the enteric-coated preparation well avoids the problem;

chinese patent CN101953802B discloses a lansoprazole enteric preparation and a preparation method thereof, the enteric preparation is prepared from the following raw materials in parts by weight, 80 parts of blank pill core and a drug layer: 20 parts of lansoprazole, 2.5 parts of magnesium oxide or magnesium carbonate, 4.0 parts of poloxamer, 2.5 parts of micronized crospovidone, 10 parts of polyvinylpyrrolidone and an isolating layer: 1.6 parts of talcum powder, 4.9 parts of titanium dioxide, 5.4 parts of polyvinylpyrrolidone, and an enteric coating layer: the enteric preparation prepared by the invention has high drug dissolution rate and reduces the dosage of a solubilizer, but the enteric preparation prepared by the invention has general stability, partial disintegration of the drug can occur when the preparation is eroded by gastric juice, so that effective substances are decomposed, the treatment effect of the drug is reduced, and the enteric preparation is not suitable for long-term storage and has poor market prospect.

Disclosure of Invention

The invention aims to provide an ipiprazine enteric-coated preparation, which is improved aiming at the defects of common enteric-coated preparations in the current market, and the ipiprazine raw material medicine is synthesized in the process of preparing the enteric-coated preparation and is produced by a chemical synthesis and high performance liquid chromatography separation refining process.

The technical problems to be solved by the invention are as follows:

1. common enteric-coated preparations in the market are eroded by gastric juice in the using process, and the enteric-coated preparations can be disintegrated to a certain degree, so that the active ingredients in the enteric-coated preparations are partially dispersed in the stomach, the normal drug effect cannot be achieved, the treatment course of using the medicine by patients is increased, and the market popularization is not facilitated;

2. common enteric-coated preparations on the market have general stability, and can be stored for a long time under specific conditions, so that the enteric-coated preparations deteriorate in the processes of production, transportation and storage, and the curative effect of the medicine is reduced or even ineffective;

3. the preparation process of common enteric-coated preparations on the market is complex, tablets need to be tabletted in the preparation process to prepare tablet cores, the tablet cores prepared by the traditional tablet core tabletting device have partial raw material waste in the charging process, the production cost is increased, and meanwhile, the tablet cores are pressed out, so that the quality of the tablet cores is different, and the tablet cores pressed out are easy to break.

The purpose of the invention can be realized by the following technical scheme:

an enteric preparation of ipipimu peptide is prepared from the following raw materials in parts by weight: 15-20 parts of ipipium caput-medusae raw material medicine, 1.5-2 parts of dextrin, 1-1.5 parts of calcium sulfate, 1.8-2 parts of starch, 0.1-0.5 part of talcum powder, 2-2.5 parts of starch slurry, 4-5.3 parts of cross-linked sodium carboxymethylcellulose, 0.5-1 part of acrylic resin I, 0.5-1 part of acrylic resin II, 12-15 parts of ethanol solution, 0.2-0.4 part of propylene glycol, 0.3-0.5 part of castor oil, 0.1-0.5 part of magnesium stearate and 0.03-0.05 part of Chinese wax;

further, the enteric preparation of the ipipimaric peptide is prepared by the following steps:

step S1: adding the illipe bulk drug, dextrin, calcium sulfate, starch and talcum powder into a pulverizer, pulverizing, sieving with a 80-100 mesh sieve, adding the illipe bulk drug, dextrin, calcium sulfate and starch into a mixer, mixing for 5-10min to obtain a first mixture, adding the first mixture and starch slurry into a stirring kettle, and stirring at the rotation speed of 500 plus 800r/min for 20-30min to obtain a soft material;

step S2: adding the soft material prepared in the step S1 into a dryer, drying for 30-40min under the condition of strong wind drying at the temperature of 60-70 ℃, sieving with a 15-24 mesh sieve to obtain solid particles, adding the solid particles, talcum powder and croscarmellose sodium into a mixer, mixing for 5-10min to obtain a second mixture, and adding the second mixture into a rotary tablet press to obtain a tablet core;

step S3: adding acrylic resin I type, acrylic resin II type and ethanol solution into a stirring kettle, stirring for 15-20min under the condition of the rotating speed of 500 plus 800r/min, adding propylene glycol and castor oil after the acrylic resin I type and the acrylic resin II type are completely dissolved, stirring for 20-30min under the condition of the rotating speed of 500 plus 800r/min, and adding magnesium stearate in the stirring process to prepare coating liquid;

step S4: adding the tablet core prepared in the step S2 into a coating pan, heating for 3-5min at the rotating speed of 2-3r/min and the air inlet temperature of 70-80 ℃, adding the coating liquid prepared in the step S4 into a spray gun, coating the tablet core, increasing the rotating speed of the coating pan to 5-10r/min after a thin layer appears on the surface of the tablet core, continuing coating the tablet core until the coating liquid is used up, blowing cold air until the air outlet temperature reaches 35-40 ℃, stopping blowing, adding Chinese wax into the coating pan, polishing for 15-20min at the rotating speed of 10-15r/min, and preparing the ipipidine enteric-coated preparation.

Further, the mass fraction of ethanol in the ethanol solution is 90-95%.

Further, the ipipimib peptide bulk drug is prepared by the following steps:

a1: adding CTC resin and DMF into a reaction kettle, soaking for 30-40min to fully expand the CTC resin, and removing redundant DMF to obtain activated CTC resin;

a2: adding the activated CTC resin prepared in the step A1, amino acid protected by Fmoc, DIC and HOBt into a reaction kettle, sequentially coupling and adding corresponding amino acid on the resin from the C-end according to an Epiputamide amino acid sequence, filtering to remove reaction liquid after all peptide chains are coupled to prepare an intermediate A, washing the intermediate A with isoamyl alcohol for 1-2 times, draining the isoamyl alcohol, washing the intermediate A with DMF for 2-3 times, and draining the DMF to obtain an intermediate B;

a3: adding the intermediate B, TFA obtained in the step A2, phenol, water, thioanisole and EDT into a reaction kettle, reacting for 2-3 hours at the temperature of 25-30 ℃, filtering, removing filter residues to obtain an intermediate C, adding the intermediate C and diethyl ether into the reaction kettle, stirring for 5-10 minutes at the rotation speed of 300r/min, filtering, and removing filtrate to obtain a crude product of the ipipimenta peptide;

a4: adding the crude product of the ipipikumicin into a preparative high performance liquid chromatograph, collecting components with purity over 90% in an elution process to obtain the ipipikumicin, adding the ipipikumicin and DCM into a stirring kettle, stirring for 3-5min under the condition of the rotation speed of 100-.

Further, the amino acid sequence of the ipipimu peptide is as follows: NH (NH)₂-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-Met-Met-Pro-Tyr-Ser-Thr-Glu-Leu-Ile-Phe-Tyr-Ile-Glu-Met-Asp-Pro-COOH。

Further, the ratio of the amount of DMF used in step a1 to the amount of DMF used in step a2 is 1: 1, the dosage ratio of DIC and HOBt in the step A2 is 10: 1, the dosage ratio of TFA, phenol, water, thioanisole and EDT in the step A3 is 82.5: 5: 5: 5: 2.5.

further, the rotary tablet press of step S2, including the box, add the feed bin, the scraper blade, the feed chute, the inside bottom of box is equipped with the rotor, the upper end of rotor is equipped with the fixed disk, the upper surface of fixed disk is equipped with the kicking block, the inside top of box is equipped with the fixed column, be equipped with the pressure disk on the fixed column, be equipped with the axis of rotation between fixed disk and the fixed column, the axis of rotation lower extreme passes the fixed disk, the axis of rotation lower extreme and the output end fixed connection of rotor, the axis of rotation is equipped with top rotating disk, well rotating disk, lower rotating disk from top to bottom in proper order, lower rotating disk is located the top of fixed disk, top rotating disk is equipped with a plurality of upper punch rods, upper punch rods are arranged in the form of ring, well rotating disk is opened and is;

the feeding bin is positioned on one side of the box body, the lower part of the feeding bin is provided with a sharp mouth part, the sharp mouth part penetrates through the side wall of the box body to enable the feeding bin to be communicated with the interior of the box body, the bottom end of the sharp mouth part is provided with a blanking disc, the upper surface of the blanking disc is provided with a first micro motor, the blanking disc is provided with a blanking disc opening, a blanking ring is arranged inside the blanking disc opening, the outer side surface of the blanking ring is provided with a plurality of gear teeth, the inner side of the blanking ring is provided with a cross-shaped scraping plate, the interior of the blanking disc is provided with a transmission gear, an output shaft of the first micro motor extends into the blanking disc, the output shaft of the first;

the scraper blade is located one side of box, and the scraper blade passes the lateral wall of box, and the inner of scraper blade is located between upper punch rod and the lower punch rod, and inner one side of scraper blade is equipped with the second micro motor, and the output shaft of second micro motor stretches fixedly connected with transfer line, and the transfer line passes the scraper blade, is equipped with the scraper blade on the transfer line, and unloading trench is located one side of box, and the unloading trench passes the lateral wall of box and makes box and outside intercommunication, and the inner of unloading trench is laminated with the lateral wall of well carousel.

Further, the number of the lower stamping rod, the stamping hole and the upper stamping rod is the same, the lower stamping rod, the stamping hole and the upper stamping rod are matched, the outer periphery of the fixing column is provided with an annular slide rail, and the upper stamping rod moves along the track of the annular slide rail.

Furthermore, the aperture of the sharp mouth opening of the sharp mouth part is the same as the aperture of the blanking disc opening, the aperture of the sharp mouth opening of the sharp mouth part is matched with the blanking disc opening, the sharp mouth part is attached to the blanking disc, the inner diameter A of the blanking ring is the same as the aperture of the blanking disc opening, the blanking ring is in running fit with the blanking disc opening, and the gear teeth are positioned inside the blanking disc opening.

Furthermore, the scraping plate and the feeding bin are respectively positioned at two sides of the box body, the scraping plate and the blanking groove are positioned at the same side, and the scraping plate is positioned above the blanking groove.

The invention has the beneficial effects that:

1. the invention prepares an Epiputitine raw material drug in the process of preparing an Epiputitine enteric-coated preparation, the Epiputitine raw material drug has the function of specifically blocking the signal transmission of p55PIK, so that the cell cycle stop participating in inflammation and the generation and secretion of various inflammatory factors are inhibited, the inflammation process can be effectively blocked, the Epiputitine only inhibits cell division, promotes cell differentiation, does not influence cell death or apoptosis, the drug prepared by taking Epiputitine as a raw material is safe and effective, does not cause injury to human body, meanwhile, the Epiputitine acts on the cell cycle and differentiation process and NF-kappa B activation process, and the processes are main reasons for the occurrence and development of various diseases including tumor and inflammatory diseases, therefore, the Epiputitine raw material drug has curative effect on almost all inflammatory diseases including in vivo inflammation such as rheumatoid arthritis, the preparation method has the advantages that the raw material medicine is produced by the aid of chemical synthesis and high performance liquid chromatography separation refining processes, biological activity is stable, a pilot test process is simple, cost is low, the ipiprazole peptide enteric preparation is not disintegrated when being eroded by gastric juice and is rapidly disintegrated when being eroded by intestinal juice, absorption of effective substances is facilitated, and meanwhile, the ipiprazole peptide enteric preparation is high in stability, can be stored for a long time, is common in raw materials and is suitable for large-scale production;

2. the invention uses a rotary tablet press in the process of preparing an ipiprazole enteric preparation, the rotary tablet press comprises a box body, a feeding bin, a scraping plate and a blanking groove, the lower part of the feeding bin is provided with a sharp mouth part, the bottom end of the sharp mouth part is provided with a blanking disc, the upper surface of the blanking disc is provided with a first micro motor, the blanking disc is provided with a blanking disc opening, a blanking ring is arranged inside the blanking disc opening, the outer side surface of the blanking ring is provided with a plurality of gear teeth, the inner side of the blanking ring is provided with a cross scraping plate, the inner part of the blanking disc is provided with a transmission gear, the output shaft of the first micro motor extends into the blanking disc, the output shaft of the first micro motor is fixedly connected with the center of the transmission gear, the transmission gear is meshed with the gear teeth, the cross scraping plate rotates to enable a second mixture to rapidly enter a stamping hole, the second mixture is uniformly stacked in the stamping hole to, and meanwhile, the redundant second mixture is scraped to the inside of the blanking ring for the next punching hole to use, so that the raw material is prevented from being wasted, a second micro motor is arranged on one side of the scraper plate, the output shaft of the second micro motor extends to be fixedly connected with the transmission rod, the transmission rod penetrates through the scraper plate, a scraper plate is arranged on the transmission rod, the tablet core can be scraped from the lower pressing rod by the rotation of the scraper plate, the scraper plate effectively accelerates the collection speed of the tablet core, meanwhile, the tablet core is prevented from being accumulated on the middle rotating disc to influence the collection of the tablet core, the preparation efficiency of the tablet core is improved, and the preparation efficiency of the enteric-coated preparation.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art that other drawings can be obtained according to the drawings without creative efforts.

Fig. 1 is a schematic view of a rotary tablet press according to the present invention;

FIG. 2 is a top view of a middle rotary plate and a lower plate of the rotary tablet press of the present invention;

FIG. 3 is a schematic structural diagram of a lower tray of the rotary tablet press of the present invention;

FIG. 4 is a schematic view of the blanking ring of the rotary tablet press of the present invention;

fig. 5 is a schematic view of the structure of a scraper blade in the rotary tablet press of the present invention.

In the figure: 1. a box body; 11. a rotator; 12. a rotating shaft; 13. fixing the disc; 131. a top block; 14. a downward rotation turntable; 141. a lower punch rod; 15. a middle rotary table; 151. punching a hole; 16. rotating the turntable upwards; 161. an upper punch rod; 162. an annular slide rail; 17. fixing a column; 18. a platen; 2. a feeding bin; 21. a nib part; 22. discharging a material tray; 221. a first micro motor; 222. a blanking disc opening; 23. a blanking ring; 231. gear teeth; 232. a cross-shaped scraper; 24. a transmission gear; 3. a blade plate; 31. a second micro motor; 32. a transmission rod; 33. a squeegee; 4. and (4) discharging the trough.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1

An enteric preparation of ipipimu peptide is prepared from the following raw materials in parts by weight: 15 parts of an ipipium peptide raw material medicine, 1.5 parts of dextrin, 1 part of calcium sulfate, 1.8 parts of starch, 0.1 part of talcum powder, 2 parts of starch slurry, 4 parts of cross-linked sodium carboxymethyl cellulose, 0.5 part of acrylic resin I, 0.5 part of acrylic resin II, 12 parts of ethanol solution, 0.2 part of propylene glycol, 0.3 part of castor oil, 0.1 part of magnesium stearate and 0.03 part of Chinese wax;

the enteric preparation of the ipipimava peptide is prepared by the following steps:

The raw material drug of the ipipimu peptide is prepared by the following steps:

a2: adding the activated CTC resin prepared in the step A1, amino acid protected by Fmoc, DIC and HOBt into a reaction kettle, reacting for 1-1.5h at the temperature of 25-30 ℃, filtering to remove reaction liquid to prepare an intermediate A, washing the intermediate A with isoamyl alcohol for 1-2 times, draining the isoamyl alcohol, washing the intermediate A with DMF for the second time, washing for 2-3 times, and draining the DMF to obtain an intermediate B;

a3: adding the intermediate B, TFA obtained in the step A2, phenol, water, thioanisole and EDT into a reaction kettle, reacting for 2-3 hours at the temperature of 25-30 ℃, filtering, removing filter residues to obtain an intermediate C, adding the intermediate C and diethyl ether into the reaction kettle, stirring for 5-10 minutes at the rotation speed of 100-300r/min, filtering, and removing filtrate to obtain an intermediate D;

a4: adding the intermediate D into a preparative high performance liquid chromatograph, collecting components with the purity of more than 90% in the elution process to obtain an intermediate E, adding the intermediate E and DCM into a stirring kettle, stirring for 3-5min under the condition of the rotation speed of 100 plus materials for 300r/min until the intermediate E is completely dissolved, adding sodium hydroxide, stirring for 5-10min under the condition of the rotation speed of 300 plus materials for 500r/min, filtering, removing filtrate, washing for 1-2 times by deionized water, adding acetic acid for salt conversion to obtain an intermediate F, adding the intermediate F into a freeze dryer, and freezing to obtain the ipipiau peptide bulk drug.

Example 2

An enteric preparation of ipipimu peptide is prepared from the following raw materials in parts by weight: the medicine comprises 18 parts of ipipium caput-medusae raw material medicine, 1.7 parts of dextrin, 1.3 parts of calcium sulfate, 1.9 parts of starch, 0.3 part of talcum powder, 2.3 parts of starch slurry, 4.5 parts of cross-linked sodium carboxymethyl cellulose, 0.7 part of acrylic resin I type, 0.3 part of acrylic resin II type, 13.5 parts of ethanol solution, 0.3 part of propylene glycol, 0.4 part of castor oil, 0.3 part of magnesium stearate and 0.04 part of Chinese wax;

Example 3

An enteric preparation of ipipimu peptide is prepared from the following raw materials in parts by weight: 20 parts of an ipipium peptide raw material drug, 2 parts of dextrin, 1.5 parts of calcium sulfate, 2 parts of starch, 0.5 part of talcum powder, 2.5 parts of starch slurry, 5.3 parts of cross-linked sodium carboxymethyl cellulose, 1 part of acrylic resin I, 1 part of acrylic resin II, 15 parts of ethanol solution, 0.4 part of propylene glycol, 0.5 part of castor oil, 0.5 part of magnesium stearate and 0.05 part of Chinese wax;

Comparative example 1

The comparative example is a common anti-inflammatory preparation on the market.

The formulations prepared in examples 1 to 3 and comparative example 1 were tested, and the test results are as follows;

buffer release rate: taking the preparations prepared in examples 1-3 and comparative example 1 respectively, according to a release degree measurement method in the second method (2) of appendix X D of the second part of 2010 edition of Chinese pharmacopoeia, adopting a dissolution degree measurement method first method device, taking 0.1mol/L hydrochloric acid solution 1000 as a solvent, rotating at 100r/min, operating according to the method, immediately lifting a rotating basket out of a liquid surface after 2 hours, observing whether the surface of the preparation has cracks or disintegration phenomena, if the phenomena appears, determining that the preparation is unqualified, if the phenomena does not appear, continuing to test, immersing the rotating basket into 1000mL phosphate buffer solution with pH8.0, rotating at a constant speed, continuing to operate according to the method, taking out the solution after 45 minutes, filtering, taking the filtrate as a test sample solution, according to a spectrophotometry method in the appendix IVA of the second part of 2010 edition of Chinese pharmacopoeia, measuring the absorbance at a wavelength of 273nm, calculating the release degree of the preparation according to an absorption coefficient of 275 of C16H1304CL2N, the results are given in table 1 below;

TABLE 1

5min

10min

15min

20min

25min

30min

45min

Example 1

11.25％

32.85％

52.14％

76.83％

88.24％

96.87％

99.86％

Example 2

10.68％

34.24％

53.66％

78.41％

85.39％

98.33％

99.54％

Example 3

11.32％

34.62％

53.42％

77.67％

86.28％

98.54％

99.93％

Comparative example 1

7.24％

18.57％

22.38％

44.28％

62.39％

76.56％

85.37％

Acid resistance measurement: according to the test Method of the delayed release preparation in the United states Pharmacopeia release degree Method B, the preparation prepared in the examples 1-3 and the comparative example 1 is detected, a slurry Method device is adopted, 1000mL of hydrochloric acid solution with the concentration of 0.1mol/L is used as a dissolution medium, the rotating speed is 100r/min, the release medium in a cup is immediately discarded after 2 hours of operation according to the Method, a test piece is taken out, the residual acid solution is washed away by water, whether the surface of the preparation has cracks or disintegration phenomenon is judged, if the phenomenon appears, the preparation is unqualified, and if the phenomenon does not appear, the content of the residual medicine in the preparation is measured, and the results are shown in the following table 2;

TABLE 2

	Traits	Degree of release in acid	Simple impurity	Total miscellaneous
					Example 1	White colour	0.85％	0.046％	0.195％
Example 2	White colour	0.77％	0.051％	0.214％
					Example 3	White colour	0.79％	0.043％	0.216％
Comparative example 1	Off-white color	1.57％	0.124％	0.348％

It can be seen from table 1 and table 2 above that the dissolution effect of the enteric preparation prepared in examples 1-3 is better than that of comparative example 1, and the acid resistance of the enteric preparation prepared in examples 1-3 is better than that of comparative example 1, and the enteric preparation of the present invention does not disintegrate when it is eroded by gastric juice, only a very small amount of medicinal substance is released, and disintegrates rapidly when it is eroded by intestinal juice, and a large amount of medicinal substance is released, facilitating the absorption of the medicinal substance, and the preparation has high stability and can be stored for a long period of time.

Referring to fig. 1-5, the rotary tablet press used in the above embodiment includes a case 1, a feeding bin 2, a scraper 3, and a discharging chute 4, wherein a rotator 11 is disposed at the bottom inside the case 1, a fixed disk 13 is disposed at the upper end of the rotator 11, a top block 131 is disposed on the upper surface of the fixed disk 13, a fixed column 17 is disposed at the top inside the case 1, a platen 18 is disposed on the fixed column 17, a rotating shaft 12 is disposed between the fixed disk 13 and the fixed column 17, the lower end of the rotating shaft 12 penetrates through the fixed disk 13, the lower end of the rotating shaft 12 is fixedly connected to the output end of the rotator 11, the rotating shaft 12 is sequentially provided with an upper rotating disk 16, a middle rotating disk 15, and a lower rotating disk 14 from top to bottom, the lower rotating disk 14 is located above the fixed disk 13, the upper rotating disk 16 is provided with a plurality of upper pressing rods 161, the upper pressing rods 161 are annularly, the lower punch rods 141 are annularly arranged;

the feeding bin 2 is positioned at one side of the box body 1, the lower part of the feeding bin 2 is provided with a sharp mouth part 21, the sharp mouth part 21 penetrates through the side wall of the box body 1 to enable the feeding bin 2 to be communicated with the inside of the box body 1, the bottom end of the sharp mouth part 21 is provided with a blanking disc 22, the upper surface of the blanking disc 22 is provided with a first micro motor 221, a blanking disc opening 222 is formed in the blanking disc 22, a blanking ring 23 is arranged inside the blanking disc opening 222, the outer side surface of the blanking ring 23 is provided with a plurality of gear teeth 231, the inner side of the blanking ring 23 is provided with a cross scraper 232, a transmission gear 24 is arranged inside the blanking disc 22, an output shaft of the first micro motor 221 extends inside the blanking disc 22, the output shaft of the first micro motor 221 is fixedly connected with;

the scraper blade 3 is located one side of box 1, the scraper blade 3 passes the lateral wall of box 1, the inner of scraper blade 3 is located between upper punch rod 161 and lower punch rod 141, inner one side of scraper blade 3 is equipped with second micro motor 31, the output shaft of second micro motor 31 stretches fixedly connected with transfer line 32, transfer line 32 passes scraper blade 3, be equipped with scraper blade 33 on the transfer line 32, the feed chute 4 is located one side of box 1, the lateral wall that the feed chute 4 passed box 1 makes box 1 and outside intercommunication, the inner of feed chute 4 is laminated with the lateral wall of well carousel 15.

The number of the lower stamping rods 141, the stamping holes 151 and the upper stamping rods 161 is the same, the lower stamping rods 141, the stamping holes 151 and the upper stamping rods 161 are matched, the outer periphery of the fixing column 17 is provided with an annular slide rail 162, and the upper stamping rods 161 move along the track of the annular slide rail 162.

The diameter of the sharp mouth part 21 is the same as the aperture of the blanking disc opening 222, the diameter of the sharp mouth part 21 is matched with the blanking disc opening 222, the sharp mouth part 21 is attached to the blanking disc 22, the inner diameter A of the blanking ring 23 is the same as the aperture of the blanking disc opening 222, the blanking ring 23 is rotationally matched with the blanking disc opening 222, and the gear teeth 231 are located inside the blanking disc opening 222.

The scraping plate 3 and the feeding bin 2 are respectively positioned at two sides of the box body 1, the scraping plate 3 and the blanking slot 4 are positioned at the same side, and the scraping plate 3 is positioned above the blanking slot 4.

The working principle is as follows: adding the second mixture into the feeding bin 2, opening the rotator 11, the first micro motor 221, the second micro motor 31, the first micro motor 221 driving the transmission gear 24 to rotate, the transmission gear 24 driving the blanking ring 23 to rotate, the blanking ring 23 driving the cross-shaped scraper 232 to rotate, the second mixture reaching the blanking ring 23 along the sharp mouth 21 to enter the punching hole 151, the cross-shaped scraper 232 rotating to make the second mixture rapidly enter the punching hole 151, and the second mixture being uniformly stacked in the punching hole 151 to prevent the second mixture from being stacked in the blanking disc opening 222, and simultaneously scraping the redundant second mixture into the blanking ring 23 for the next punching hole 151 to prevent the waste of the raw materials, when the upper punching rod 161 rotates to the lower end of the pressing disc 18, the lower end of the upper punching rod 161 completes the tabletting, when the lower punching rod 141 rotates to the top block 131, the upper core of the lower punching rod 141 pushes the lower punching rod 141 out of the punching hole 151, the scraper 33 rotates to scrape the tablet core from the lower punch rod 141, the scraper 33 can accelerate the collection speed of the tablet core, meanwhile, the tablet core is prevented from being accumulated on the middle rotary table 15 to influence the collection of the tablet core, the tablet core slides down along the blanking groove 4, the tablet core is collected, and tabletting is completed.

The foregoing is merely exemplary and illustrative of the principles of the present invention and various modifications, additions and substitutions of the specific embodiments described herein may be made by those skilled in the art without departing from the principles of the present invention or exceeding the scope of the claims set forth herein.

Claims

1. An enteric preparation of ipipimib peptide, which is characterized in that: the feed is prepared from the following raw materials in parts by weight: 15-20 parts of ipipium caput-medusae raw material medicine, 1.5-2 parts of dextrin, 1-1.5 parts of calcium sulfate, 1.8-2 parts of starch, 0.1-0.5 part of talcum powder, 2-2.5 parts of starch slurry, 4-5.3 parts of cross-linked sodium carboxymethyl cellulose, 0.5-1 part of acrylic resin I, 0.5-1 part of acrylic resin II, 12-15 parts of ethanol solution, 0.2-0.4 part of propylene glycol, 0.3-0.5 part of castor oil, 0.1-0.5 part of magnesium stearate and 0.03-0.05 part of Chinese wax.

2. An enteric ipipimib peptide formulation according to claim 1, wherein: the enteric preparation of the ipipimava peptide is prepared by the following steps:

3. An enteric ipipimib peptide formulation according to claim 1, wherein: the mass fraction of ethanol in the ethanol solution is 90-95%.

4. An enteric ipipimib peptide formulation according to claim 1, wherein: the raw material drug of the ipipimu peptide is prepared by the following steps:

5. An enteric ipipimib peptide formulation according to claim 4, wherein: the amino acid sequence of the ipipimu peptide is as follows: NH (NH)₂-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-Met-Met-Pro-Tyr-Ser-Thr-Glu-Leu-Ile-Phe-Tyr-Ile-Glu-Met-Asp-Pro-COOH。

6. An enteric ipipimib peptide formulation according to claim 4, wherein: the ratio of the amount of DMF in step A1 to the amount of DMF in step A2 was 1: 1, the dosage ratio of DIC and HOBt in the step A2 is 10: 1, the dosage ratio of TFA, phenol, water, thioanisole and EDT in the step A3 is 82.5: 5: 5: 5: 2.5.

7. an enteric ipipimib peptide formulation according to claim 1, wherein: step S2 the rotary tablet press comprises a box body (1), a feeding bin (2), a scraper plate (3) and a blanking groove (4), wherein a rotator (11) is arranged at the bottom end inside the box body (1), a fixed disc (13) is arranged at the upper end of the rotator (11), a top block (131) is arranged on the upper surface of the fixed disc (13), a fixed column (17) is arranged at the top end inside the box body (1), a pressure plate (18) is arranged on the fixed column (17), a rotating shaft (12) is arranged between the fixed disc (13) and the fixed column (17), the lower end of the rotating shaft (12) penetrates through the fixed disc (13), the lower end of the rotating shaft (12) is fixedly connected with the output end of the rotator (11), an upper rotating disc (16), a middle rotating disc (15) and a lower rotating disc (14) are sequentially arranged on the rotating shaft (12) from top to bottom, the lower rotating disc (14) is positioned above the, the upper punching rods (161) are annularly arranged, the middle rotary table (15) is provided with a plurality of punching holes (151), the lower rotary table (14) is provided with a plurality of lower punching rods (141), and the lower punching rods (141) are annularly arranged;

the feeding bin (2) is located on one side of the box body (1), a sharp opening part (21) is arranged on the lower portion of the feeding bin (2), the sharp opening part (21) penetrates through the side wall of the box body (1) to enable the feeding bin (2) to be communicated with the interior of the box body (1), a blanking disc (22) is arranged at the bottom end of the sharp opening part (21), a first micro motor (221) is arranged on the upper surface of the blanking disc (22), a blanking disc opening (222) is formed in the blanking disc (22), a blanking ring (23) is arranged in the blanking disc opening (222), a plurality of gear teeth (231) are arranged on the outer side surface of the blanking ring (23), a cross scraper (232) is arranged on the inner side of the blanking ring (23), a transmission gear (24) is arranged in the blanking disc (22), an output shaft of the first micro motor (221) extends into the lower disc (22), the output shaft of the first micro motor (221) is fixedly connected with the center of the transmission gear (24), and;

the scraper blade (3) is located one side of box (1), the lateral wall of box (1) is passed in scraper blade (3), the inner of scraper blade (3) is located between upper punch rod (161) and lower punch rod (141), inner one side of scraper blade (3) is equipped with second micro motor (31), the output shaft of second micro motor (31) stretches fixedly connected with transfer line (32), transfer line (32) pass scraper blade (3), be equipped with scraper blade (33) on transfer line (32), lower silo (4) are located one side of box (1), lower silo (4) pass the lateral wall of box (1) make box (1) and outside intercommunication, the inner of lower silo (4) and the lateral wall laminating of mesowhirl dish (15).

8. An enteric ipipimib peptide formulation according to claim 7, wherein: the number of the lower punching rods (141), the punching holes (151) and the upper punching rods (161) is the same, the lower punching rods (141), the punching holes (151) and the upper punching rods (161) are matched, the outer periphery of the fixing column (17) is provided with an annular slide rail (162), and the upper punching rods (161) move along the track of the annular slide rail (162).

9. An enteric ipipimib peptide formulation according to claim 7, wherein: the aperture of the sharp mouth part (21) is the same as the aperture of the blanking disc opening (222), the aperture of the sharp mouth part (21) is matched with the blanking disc opening (222), the sharp mouth part (21) is attached to the blanking disc (22), the inner diameter A of the blanking ring (23) is the same as the aperture of the blanking disc opening (222), the blanking ring (23) is in running fit with the blanking disc opening (222), and the gear teeth (231) are located inside the blanking disc opening (222).

10. An enteric ipipimib peptide formulation according to claim 7, wherein: the scraper blade (3) and the feeding bin (2) are respectively positioned at two sides of the box body (1), the scraper blade (3) and the feeding trough (4) are positioned at the same side, and the scraper blade (3) is positioned above the feeding trough (4).